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Evaluation of the Safety and Tolerability of i.v. Administration of a Cancer Vaccine in Patients With Advanced Melanoma (Lipo-MERIT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02410733
Recruitment Status : Active, not recruiting
First Posted : April 8, 2015
Last Update Posted : October 13, 2021
Information provided by (Responsible Party):
BioNTech SE ( BioNTech RNA Pharmaceuticals GmbH )

Brief Summary:
The purpose of this study is to determine the safety and tolerability of intravenous administration of a tetravalent RNA-lipoplex cancer vaccine targeting four tumor-associated antigens in patients with advanced melanoma.

Condition or disease Intervention/treatment Phase
Melanoma Biological: Lipo-MERIT Phase 1

Detailed Description:
  • The Lipo-MERIT vaccine consists of the four naked ribonucleic acid (RNA)-drug products (DPs) RBL001.1, RBL002.2, RBL003.1, and RBL004.1 that are optimised to induce antigen-specific CD8+ and CD4+ T cell responses against four selected malignant melanoma-associated antigens respectively.
  • In this study, naked RNA DPs will be formulated with liposomes to form RNA-lipoplexes (RNA(LIP)) that (i) protect RNA from degradation in the serum, (ii) enable in vivo targeting of systemic antigen-presenting cells (APC), and therefore (iii) constitute a novel vaccine formulation that supports intravenous administration.
  • The Lipo-MERIT vaccine is expected to lead to several effects contributing to its immunological (therapeutic) effect. First, the RNA-lipoplexes home to APCs in lymphoid organs after intravenous injection, where they are rapidly taken up by professional APCs. Incorporated RNA is translocated to the cytoplasm leading to its translation by the host ribosome complex into four Antigen encoding proteins which are processed and presented on both HLA-class I as well as HLA-class II molecules. Consecutively, antigen-specific CD8+ and CD4+ T cell responses will be triggered by HLA-peptide complexes on the surface of antigen-presenting cells.
  • In addition, the Lipo-MERIT vaccine is expected to transiently activate APCs (change of surface marker expression and cytokine secretion) via signalling of TLRs, subsequently leading to the transient induction of inflammatory cytokines (such as IFN-α and IP-10) supporting the induction of tumour-antigen specific T cell responses.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 119 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Clinical First-in-human Dose Escalation Study Evaluating the Safety and Tolerability of Intravenous Administration of a Tetravalent RNA-lipoplex Cancer Vaccine Targeting Four Tumour-associated Antigens in Patients With Advanced Melanoma
Actual Study Start Date : March 2015
Estimated Primary Completion Date : May 2023
Estimated Study Completion Date : May 2023

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: Lipo-MERIT
7 dose escalation cohorts (3 +3 design) and 3 expanded cohorts
Biological: Lipo-MERIT

Primary Outcome Measures :
  1. Number of Adverse Events as a Measure of safety and tolerability [ Time Frame: 180 days ]
    Number of patients with adverse events, total number of adverse events, dose limiting toxicities

Secondary Outcome Measures :
  1. Change of induced T-cell responses for Lipo-MERIT vaccine from visit 2 (day 1) to day 71 (assessed by immunoassays) [ Time Frame: 90 days ]
    Vaccine induced T-cell responses assessed by immunoassays in peripheral blood and skin

  2. Clinical Monitoring of tumor lesions (determined by CT or MRI results evaluated by irRECIST 1.1) [ Time Frame: 90 days ]
    Tumour lesion status as determined by CT or MRI results evaluated by irRECIST 1.1

  3. Progression Free Survival (PFS) [ Time Frame: every 3 month, From Baseline until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months ]
    Defined as the time from the first vaccination to confirmed occurence of Progression or death from any course, which ever occurs first, per irRECIST 1.1

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Cohort I: stage IV malignant melanoma (AJCC 2009 melanoma classification)
  • Cohorts II-VII end expanded cohorts: stage IIIB-C, or stage IV of malignant melanoma (AJCC 2009 melanoma classification) Expanded cohorts C only patients with stage IV melanoma (AJCC 2009 melanoma classification) with measurable disease (at least one target lesion according irRECIST 1.1) [applicable for all patients after approval of protocol version 10.0]
  • Therapy only for subjects not eligible or declining any other available approved therapy after all available treatment options have been transparently disclosed (to be documented!)
  • Expression of either one of four TAA confirmed by RT-qPCR analysis from FFPE
  • ≥ 18 years of age
  • Written informed consent
  • ECOG performance status (PS) 0-1
  • Life expectancy >/= 6 months
  • WBC ≥ 3x10E9/L
  • Hemoglobin ≥ 9 g/dL
  • Platelet count ≥ 100,000/mm³
  • ALT/AST < 3 x ULN (except patients with liver metastasis)
  • Negative pregnancy test (measured by β-HCG) for females with childbearing age

Exclusion Criteria:

  • Pregnancy or breastfeeding
  • Primary ocular melanoma
  • Concurrence of a second malignancy other than squamous or basal cell carcinoma, non-active prostate cancer, or cervical carcinoma in situ or non-active treated urothelial carcinoma
  • Brain metastases

    • Patients with history of treated or inactive brain metastasis are eligible for treatment in expanded cohort C, provided they meet all of the following criteria:
    • measurable disease outside of the brain (in addition to inactive brain metastasis);
    • no ongoing requirement of corticosteroids as therapy for brain metastases,
    • with corticosteroids discontinued ≥1 week prior to visit 2 (day 1) with no ongoing symptoms attributable to brain metastasis;
    • the screening brain radiographic imaging is ≥ 4 weeks since completion of radiotherapy
  • Post-splenectomy Patients
  • Known hypersensitivity to the active substance or to any of the excipients
  • A serious local infection (e.g. cellulitis, abscess) or systemic infection (e.g. pneumonia, septicemia) which requires systemic antibiotic treatment within 2 weeks prior to the first dose of study medication
  • Positive test for acute or chronic active hepatitis B or C infection
  • Clinically relevant active autoimmune disease
  • Systemic immune suppression:

    • HIV disease
    • Use of chronic oral or systemic steroid medication (topical or inhalational steroids are permitted)
    • Other clinical relevant systemic immune suppression
  • Symptomatic congestive heart failure (NYHA 3 or 4)
  • Unstable angina pectoris
  • Radiotherapy and minor surgery within 14 days prior to the first study treatment administration
  • Myelosuppressive chemotherapy within 14 days and after reconstitution of blood values prior to the first study treatment administration
  • Ipilimumab within 28 days prior to the first study treatment administration
  • Treatments with BRAF inhibitors, MEK inhibitors, or the combination of both, and anti-PD-1 antibodies within 14 days prior to the first administration of study treatment (not applicable for patients with parallel treatment in expanded cohorts A, B, or C at the discretion of the investigator)
  • Interferon, major surgery, vaccination, and other investigational agents within 28 days or 5 half-lives depending on what gives the longer range before the first treatment
  • Approved BRAF inhibitors vemurafenib or dabrafenib, approved anti-PD-1 inhibitors nivolumab or pembrolizumab as well as approved MEK inhibitor trametinib, or the approved combination of BRAF-MEK inhibitors in patients in dose escalation cohorts. Concomitant treatment with approved BRAF inhibitors, approved anti-PD-1 antibodies or MEK inhibitor as well as the approved combination of BRAF-MEK inhibitors is allowed for patients included in the expanded cohorts, after analysis of safety data collected for the dose escalation cohorts and DSMB approval. Local radiation will be allowed as concurrent treatment for patients in expanded cohort as well.

    - After approval of protocol version 10.0 only anti-PD-1 antibodies are allowed for treatment of patients in expanded cohort C.

  • Fertile males and females who are unwilling to use a highly effective method of birth control (less than 1% per year, e.g. condom with spermicide, diaphragm with spermicide, birth control pills, injections, patches or intrauterine device) during study treatment and for at least 28 days (male patients) and 90 days (female patients of childbearing potential)after the last dose of study treatment
  • Presence of a severe concurrent illness or other condition (e.g. psychological, family, sociological, or geographical circumstances) that does not permit adequate follow-up and compliance with the protocol

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02410733

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Johann Wolfgang Goethe Universität Frankfurt, Klinik für Dermatologie, Venerologie und Allergologie
Frankfurt, Germany, 60590
Universität Heidelberg, Dermatologie und NCT
Heidelberg, Germany, 69120
Universitätsmedizin Mainz, Hautklinik und Poliklinik
Mainz, Germany, 55131
Universitätsmedizin Mannheim, Klinik für Dermatologie, Venerologie und Allergologie
Mannheim, Germany, 68167
Sponsors and Collaborators
BioNTech RNA Pharmaceuticals GmbH
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Study Director: BioNTech Responsible Person BioNTech SE
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: BioNTech RNA Pharmaceuticals GmbH Identifier: NCT02410733    
Other Study ID Numbers: RB_0003-01
First Posted: April 8, 2015    Key Record Dates
Last Update Posted: October 13, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by BioNTech SE ( BioNTech RNA Pharmaceuticals GmbH ):
cancer vaccine
BioNTech RNA Pharmaceuticals
BioNTech RNA
RNA vaccine
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas